<scp>MASK</scp>‐air® direct patient data support the <scp>ARIA‐MeDALL</scp> hypothesis on allergic phenotypes
Authors: Jean Bousquet, Bernardo Sousa‐Pinto, Frederico S. Regateiro, Ana Margarida Pereira, Luisa Brussino, Violeta Kvedariene, Désirée E. Larenas‐Linnemann, Luis Taborda‐Barata, Maria Teresa Ventura, Rafael José Vieira, Joao A. Fonseca, Torsten Zuberbier, Josep M. Anto
Journal: Allergy (2023)

The concept of 'one-airway-one-disease', based on the links between upper and lower airway allergic diseases,1 may be an oversimplification. The ARIA-MeDALL (Allergic Rhinitis and its Impact on Asthma-Mechanisms of the Development of ALLergy) hypothesis—based on genomic, epidemiologic and clinical findings—proposed that rhinitis alone (R) may be a distinct entity from rhinitis and asthma multimorbidity (A + R), with therapeutic relevance.2 However, the ARIA-MeDALL hypothesis has not been tested using real-world data. The aim of this study was therefore to assess the differences in symptoms and medications between R and A + R using data from MASK-air®, a freely available mHealth app. The methods of this study are fully described in the online supplement. Briefly, in a previous study, using k-means cluster analysis, we identified three groups of MASK-air® users: those having 'probable asthma', 'possible asthma' or 'no evidence of asthma' (R).4 In this study, we assessed MASK-air® data (2015–2020) cross-sectionally and compared patients with 'probable asthma', 'possible asthma' and 'no evidence of asthma' on (i) their maximum and median reported visual analogue scale (VAS) values for global allergy symptoms, nasal, ocular and asthma symptoms as well as on the impact of allergy on work,3 (ii) the combined symptom-medication score (allergy-CSMS5) and (iii) the medication component of the allergy-CSMS. We performed a sensitivity analysis in a sample of patients with physician-diagnosed current asthma, past asthma and no evidence of asthma. Finally, we longitudinally compared users of the three groups on the frequency of complete weeks displaying well-controlled, partly-controlled, variably-controlled or uncontrolled rhinitis. We analysed the data of 3797 patients from 25 countries (256,839 days) (Table S1 online, Figure S1 online). A total of 1733 patients provided complete weeks of MASK-air® data (14,409 weeks). Patients with 'probable asthma' or 'possible asthma' displayed meaningfully higher VAS values and allergy-CSMS than those with 'no evidence of asthma' (Table 1). The differences were moderate–high for VAS eye, asthma and work as well as for allergy-CSMS. There were meaningful differences when rhinitis treatments were compared in the three groups: patients with 'probable asthma' reported more allergy medications than those with 'possible asthma' or 'no evidence of asthma'. Robust results were obtained in the subanalysis of 282 patients enrolled by physicians (Tables S2 and S3 online). We compared allergy-CSMS levels in each country with data from >100 patients (Table 2). For maximum allergy-CSMS levels, moderate or large meaningful differences were observed for all countries when comparing 'probable asthma' versus 'no evidence of asthma'. Small meaningful differences were found for most countries when comparing 'probable asthma' and 'possible asthma'. The percentage of weeks with controlled rhinitis ranged from 62.8% ('possible asthma') to 80.0% ('no evidence of asthma'), while the percentage of weeks with partly-controlled or uncontrolled rhinitis ranged from 12.6% ('no evidence of asthma') to 27.9% ('possible asthma') (Table S4 online). In this study, using real-world data from an mHealth app, we observed that, by comparison to R, patients with 'probable asthma' display higher allergy-CSMS levels, higher VAS levels of nasal or ocular symptoms, an increased use of rhinitis medication and a higher frequency of weeks with partly-controlled or uncontrolled rhinitis. The CSMS results were individually found in different countries, suggesting the generalisability of the finding. Although some of the differences were not associated with high effect sizes and there may have been user-/day-related selection biases or some information biases (e.g. on asthma classification), these results overall support the existence of meaningful differences in rhinitis control when considering patients with A + R versus R. Overall, although not excluding other hypotheses, this study is in line with the ARIA-MeDALL hypothesis. Clinically, this study supports the assessment of the possibility of asthma in patients with more severe rhinitis. MASK-air® has been supported by EU grants (POLLAR, EIT Health; Structural and Development Funds, Twinning, EIP on AHA, H2020 and Horizon Europe) and educational grants from Mylan-Viatris, ALK, GSK, Novartis and Uriach. JB was responsible for the study design, data analysis and manuscript writing (original draft). BSP and RJV were responsible for data analysis and manuscript writing (original draft). The remaining authors were responsible for data collection and for critical revision and editing of the manuscript. None. JB reports personal fees from Cipla, Menarini, Mylan, Novartis, Purina, Sanofi-Aventis, Teva, Uriach, other from KYomed-Innov, other from MASK-air-SAS, outside the submitted work. JB owns shares in MASK-air® SAS and KYomed-Innov. VK reports other from Norameda, other from BerlinCHemie Menarini, outside the submitted work. DLL reports personal fees from ALK, Allakos, Amstrong, Astrazeneca national and global, Chiesi, DBV Technologies, Grunenthal, GSK national and global, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot, grants from Abbvie, Lilly, Sanofi, Astrazeneca, Lilly, Pfizer, Novartis, Circassia, UCB, GSK, Purina institute, outside the submitted work. FR reports personal fees from Novartis, personal fees and nonfinancial support from Sanofi, personal fees from AstraZeneca, personal fees from GSK, personal fees from Medinfar, personal fees from Azentis, from SPAIC, outside the submitted work. LTB reports personal fees from LETI, personal fees from Vitoria Laboratories, personal fees from Novartis, outside the submitted work. TZ reports grants and personal fees from Novartis, grants and personal fees from Henkel, personal fees from Bayer, personal fees from FAES, personal fees from Astra Zeneca, personal fees from AbbVie, personal fees from ALK, personal fees from Almirall, personal fees from Astellas, personal fees from Bayer, personal fees from Bencard, personal fees from Berlin Chemie, personal fees from FAES, personal fees from Hal, personal fees from Leti, personal fees from Mesa, personal fees from Menarini, personal fees from Merck, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sanofi, personal fees from Stallergenes, personal fees from Takeda, personal fees from Teva, personal fees from UCB, personal fees from Henkel, personal fees from Kryolan, personal fees from L'Oreal, outside the submitted work; and Organizational affiliations: Commitee member: WHO-Initiative 'Allergic Rhinitis and Its Impact on Asthma' (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF); President: Global Allergy and Asthma European Network (GA2LEN); Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). The other authors have no COI to disclose, outside the submitted work. Wienczyslawa Czarlewski, Anna Bedbrook, Tari Haahtela, Ludger Klimek, Oliver Pfaar, Piotr Kuna, Maciej Kupczyk, Boleslaw Samolinski, Arunas Valiulis, Rute Almeida, Cristina Jácome, Arzu Yorgancioglu, Karl-Christian Bergmann, Sinthia Bosnic-Anticevich, G Walter Canonica, Victoria Cardona, Lorenzo Cecchi, Claudia Chaves Loureiro, Alvaro A Cruz, Bilun Gemicioglu, Wytske J Fokkens, Juan Carlos Ivancevich, Helga Kraxner, Daniel Laune, Renaud Louis, Michael Makris, Mario Morais-Almeida, Joaquim Mullol, Marek Niedoszytko, Yoshitaka Okamoto, Nikolaos G Papadopoulos, Vincenzo Patella, Nhân Pham-Thi, Philip W Rouadi, Joaquin Sastre, Nicola Scichilone, Aziz Sheikh, Mikhail Sofiev, Sanna Toppila-Salmi, Ioanna Tsiligianni, Erkka Valovirta, Mihaela Zidarn, Rita Amaral, Ignacio J Ansotegui, Louis-Philippe Boulet, Guy Brusselle, Roland Buhl, Denis Charpin, Philippe Devillier, Virginie Doyen, Ewa Jassem, Guy Joos, Marek Jutel, Thomas Keil, Marek Kulus, Olga Lourenço, Ralph Mösges, Rachel Nadif, Stefania Nicola, Alberto Papi, Jean-Louis Pépin, Benoit Pétré, Francesca Puggioni, Santiago Quirce, Sietze Reitsma, Nicolas Roche, Monica Rodriguez-Gonzalez, Ana Sá-Sousa, Marine Savouré, Faradiba S Serpa, Milan Sova, Annette Sperl, y, Omar S Usmani, Peter Valentin Tomazic, Olivier Vandenplas Data sharing is not applicable to this article as no new data were created or analyzed in this study. 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